Structural and antitumor properties of the YSNSG cyclopeptide derived from tumstatin.
Fiche publication
Date publication
décembre 2006
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BRASSART-PASCO Sylvie, Pr DAUCHEZ Manuel, Dr MONBOISSE Jean-Claude, Dr NUZILLARD Jean-Marc, Pr RAMONT Laurent, Dr THEVENARD-DEVY Jessica
Tous les auteurs :
Thevenard J, Floquet N, Ramont L, Prost E, Nuzillard JM, Dauchez M, Yezid H, Alix AJ, Maquart FX, Monboisse JC, Brassart-Pasco S
Lien Pubmed
Résumé
We previously demonstrated that the NC1[alpha3(IV)185-191] CNYYSNS peptide inhibited in vivo tumor progression. The YSNS motif formed a beta turn crucial for biological activity. The aim of the present study was to design a YSNSG cyclopeptide with a constrained beta turn on the YSNS residues more stable than CNYYSNS. By nuclear magnetic resonance and molecular modeling, we demonstrated that the YSNSG cyclopeptide actually adopted the expected beta-turn conformation. It promoted melanoma cell adhesion and prevented their adhesion to the native peptide. It inhibited in vitro cell proliferation and migration through Matrigel by downregulating proteolytic cascades. Moreover, intraperitoneal administration of the YSNSG cyclopeptide inhibited melanoma progression far more efficiently than the native peptide. The increased solubility and stability at low pH of the YSNSG cyclopeptide suggest this peptide as a potent antitumor therapeutic agent.
Référence
Chem Biol. 2006 Dec;13(12):1307-15.